NSAIDs Added to Anti-TNF Therapy Versus Anti-TNF Therapy Alone on Progression of Structural Damage in Ankylosing Spondylitis

COmparison of the Effect of Treatment With NSAIDs Added to Anti-TNF Therapy Versus Anti-TNF Therapy Alone on Progression of StrUctural Damage in the Spine Over Two Years in Patients With ankyLosing Spondylitis: a Randomized Controlled Multicentre Trial

To evaluate the impact of treatment with a non-steroidal anti-inflammatory drug (NSAID) - Celecoxib - when added to anti-tumour necrosis factor (TNF) therapy - Golimumab - as compared to anti-TNF therapy (Golimumab) alone on progression of structural damage in the spine over two years in patients with ankylosing spondylitis (AS).

The aim of the proposed trial is to evaluate the efficacy of combined treatment with a non-steroidal anti-inflammatory drug (NSAID) added to anti-tumour necrosis factor (TNF) therapy as compared to anti-TNF therapy alone on progression of structural damage in the spine over two years in patients with ankylosing spondylitis (AS). The trial consists of two phases. In the phase I (run-in phase), patients with active AS despite treatment with NSAIDs and elevated C-reactive protein will be included and treated with a TNF blocker (golimumab). Patients with good clinical response to golimumab at week 12 will be eligible for the phase II (core phase) of the study and will be randomized 1:1 to 1) golimumab + celecoxib (experimental intervention) for 2 years (weeks 12-108) or 2) golimumab alone (control intervention) also for 2 years. The primary outcome parameter will be the absolute progression of the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) - currently a standard of structural spinal damage progression evaluation in AS - over two years of therapy (weeks 12-108).

Major Inclusion Criteria:

• Definite diagnosis of AS according to the "modified New York criteria".

• History of an inadequate response to ≥2 NSAIDs taken for at least 2 weeks each.

• Active disease as defined by a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) value of ≥4 at screening.

• Presence of at least one of the following risk factors for radiographic spinal progression:

  1. Elevated C reactive protein (CRP; >5mg/l) at screening at the absence of reasons for elevated CRP other than AS;
  2. Presence of ≥ 1 syndesmophyte on prior X-rays of the spine.

• Subject is a candidate for anti-TNF therapy based on the Investigator's opinion.

• Subject is able and willing to give a written informed consent and comply with the requirements of the study protocol. Only patients who give written informed consent will be included in the trial.

• If female: either unable to bear children (postmenopausal for at least 1 year or surgically sterile) or is willing and able to practice a reliable method of contraception throughout the study and 6 months after

Inclusion Criterion for Phase II (randomized part of the study):

- adequate response to Golimumab during Phase I (referred to as decline in BASDAI)

Major Exclusion Criteria:

• For female subjects: pregnancy or lactating
• subjects with chronic inflammatory articular disease other than spondyloarthritis / AS or systemic autoimmune disease, e.g. systemic lupus erythematosus, Sjögren´s syndrome, rheumatoid arthritis.
• history of inadequate response to anti-TNF-therapy
• intolerability/hypersensitivity to one of the drugs or other components of the study medication
• presence ot total spinal ankylosis
• contraindications to anti-TNF-therapy (current or remitting clinical significant infections, tuberculosis, viral hepatitis, HIV; malignancies; demyelinating disease; vaccination with live vaccine within 3 months before, during and until 6 months after study)
• (relative) contraindications to Celecoxib therapy (uncontrolled arterial hypertension, high cardiovascular risk / history of cardiovascular events; history of gastrointestinal ulcers or relevant bleeding; known M. Crohn or ulcerative colitis)
• diagnosis of fibromyalgia
• significant lab abnormalities